1. Field of the Invention
The present invention relates to the use of analogs of glutamic acid and gamma-aminobutyric acid (GABA) for treatment of renal colic.
2. Description of Related Art
GABA analogs are known agents useful in antiseizure therapy for central nervous system disorders such as epilepsy, Huntington""s chorea, cerebral ischemia, Parkinson""s disease, tardive dyskinesia, and spasticity. It has also been suggested that the compounds can be used as antidepressants, anxiolytics and antipsychotics. See WO 92/09560 (U.S. Ser. No. 618,692 filed Nov. 27, 1990) and WP 93/23383 (U.S. Ser. No. 886,080 filed May 20, 1992).
WO 97/33858 teaches that compounds related to gabapentin are useful for treating epilespy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, and neuropathological disorders. WO 97/33858 does not specify what forms of pain are treated.
Additionally, the compounds of the invention are known for treatment of neuropathic pain. For example, see Rosner H; Rubin L; Kestenbaum A., Gabapentin adjunctive therapy in neuropathic pain states. Clin J Pain, March 1996, 12:1, 56-8; Segal A Z; Rordorf G., Gabapentin as a novel treatment for postherpetic neuralgia. Neurology, April 1996, 46:4, 1175-6; Wetzel C H; Connelly J F., Use of gabapentin in pain management. Ann Pharmacother, September 1997, 31:9, 1082-3; Zapp J J., Postpoliomyelitis pain treated with gabapentin [letter]. Am Fam Physician, June 1996, 53:8, 2442, 2445; Cheville A, et al., Neuropathic pain in radiation myelopathy:a case report. Program book, American Pain Society (14th Annual Scientific Meeting). Abstract #95823, p. A-115; Sist T; Filadora V; Miner M; Lema M., Gabapentin for idiopathic trigeminal neuralgia: report of two cases. Neurology, May 1997, 48:5, 1467; Waldman S D, Tutorial 28: Evaluation and Treatment of Trigeminal Neuralgia. Pain Digest (1997) 7:21-24; Mellick L B; Mellick G A., Successful treatment of reflex sympathetic dystrophy with gabapentin [letter]. Am J Emerg Med, January 1995, 13:1, 96; Mellick G A; Seng M I., The use of gabapentin in the treatment of reflex sympathetic dystrophy and a phobic disorder. Am J Pain Manage 1995; 5:7-9; Mellick G A; Mellicy L B; Mellick L B., Gabapentin in the management of reflex sympathetic dystrophy [letter]. J Pain Symptom Manage, May 1995, 10:4, 265-6; Mellick G A; Mellick L B., Reflex sympathetic dystrophy treated with gabapentin. Arch Phys Med Rehabil, January 1997, 78:1, 98-105 and Mackin G A., Medical and pharmacologic management of upper extremity neuropathic pain syndromes. J Hand Ther, April-June 1997, 10:2, 96-109.
Renal colic is commonly known as kidney stones. The passage of these crystalline fragments is so painful that it is proverbially known as the male equivalent of xe2x80x9cchild birth or labor.xe2x80x9d Patients are in such agony, that they are often rushed to hospital emergency rooms for treatment. While not life-threatening, the pain is so incapacitating that patients are often started on narcotic pain relievers.
The typical renal colic sufferer makes an initial visit to the hospital and is given i.m. morphine or equivalent for about 48 hours after diagnosis. Then the patient is sent home on oral narcotic analgesics and ESWL (lithotripsy) is performed within 1 week. Typically all of the fragments pass at home within two weeks. The pain intensity is universally on the top of all pain scales.
According to Urinary Calculi: ESWL, Endourology, and Medical Therapy, James E. Lingeman, et.al., 1994:51-71, the incidence of kidney stones is 335,000 patients/year (ie, those who are admitted to the ER because of renal colic). According to the Merck Manual, approximately 1 in every 1000 adults is hospitalized annually in the USA because of urinary stones (which equals about 200,000 per year).
About 80% of urinary calculi, or kidney stones, are composed of Ca, mainly calcium oxalate; 5% are uric acid; 2% cystine; and the remainder, magnesium ammonium phosphate. All of these stones are crystalline in structure, often with sharp edges that resemble small pieces of broken glass. Whether the stones pass through the ureter intact and spontaneously or in fragments following extracorporeal shock wave lithotripsy, extreme pain typically accompanies ureteral passage. This pain is often only partially relieved, even with the use of narcotic analgesics like morphine.
This invention provides a method for treating renal colic comprising administering to a subject suffering from such pain an effective amount of a GABA analog. A preferred embodiment utilizes a cyclic amino acid compound of Formula I 
wherein R1 is hydrogen or lower alkyl and n is an integer of from 4 to 6, and the pharmaceutically acceptable salts thereof. An especially preferred embodiment utilizes a compound of Formula I where R1 is hydrogen and n is 4, which compound is 1-(aminomethyl)-cyclohexane acetic acid, known generically as gabapentin.
In another embodiment, the invention includes treating renal colic pain with a compound of Formula II. 
wherein R2 is a straight or branched alkyl of from 1 to 6 carbon atoms, phenyl, or cycloalkyl having from 3 to 6 carbon atoms; R3 is hydrogen or methyl; and R4 is hydrogen, methyl, or carboxyl; or an individual enantiomeric isomer thereof; or a pharmaceutically acceptable salt thereof, in unit dosage form, to a mammal in need of said treatment.
Preferred compounds of the invention are those wherein R4 and R3 are hydrogen, and R2 is xe2x80x94(CH2)0-2-iC4H9 as an (R), (S), or (R,S) isomer.
The more preferred compounds of Formula II invention are (S)-3-(aminomethyl)-5-methylhexanoic acid and 3-aminomethyl-5-methyl-hexanoic acid, now known generically as pregabalin.